Selection of Antibiotics as Prophylaxis for Close Contacts of Patients with Meningococcal Disease in Areas with Ciprofloxacin Resistance — United States, 2024

Rationale and Evidence

Invasive Meningococcal Disease Cases and Resistance Patterns

An annual average of 1.25 cases of invasive meningococcal disease caused by ciprofloxacin-resistant strains were reported in the United States during 2011–2018; however, the number of such cases has increased sharply since 2019. An annual average of 9.7 cases of invasive meningococcal disease caused by ciprofloxacin-resistant strains were reported in 2019, 2020, and 2021, despite an overall 75% decline in disease incidence from 0.24 cases per 100,000 population (2011) to 0.06 (2021) (Figure 1). Recent cases were predominantly caused by ciprofloxacin- and penicillin-resistant NmY strains and were distributed across the United States, but clusters were identified in some geographic areas (Figure 2).

Considerations in Determining Resistance Thresholds

Resistance thresholds for recommending changing antibiotics are inconsistent across pathogens and contexts (5). CDC experts agreed that, because of the severity of invasive meningococcal disease and high mortality risk in potential instances of prophylaxis failure, the threshold should be low. In determining the threshold for action, both a specific number of resistant cases (e.g., one or two) and a percentage (e.g., 20%) of all cases were needed to allow sufficient flexibility for jurisdictions with high invasive meningococcal disease incidence to act while ensuring areas with low incidence were not changing recommendations based on a single, potentially sporadic, resistant case.

Existing guidance states that rifampin (4 oral doses in 48 hours), ciprofloxacin (single oral dose), or ceftriaxone (single injection) are first-line antibiotics for meningococcal prophylaxis; a single oral dose of azithromycin has also been used in areas with ciprofloxacin-resistant strains (1). A published systematic review and meta-analysis determining effectiveness, adverse events, and development of drug resistance for different meningococcal prophylaxis regimens was used as supporting evidence for determining when to favor the use of recommended prophylaxis options other than ciprofloxacin (6). Six studies presented data on rifampin compared with placebo and found that rifampin was effective at eradicating N. meningitidis 1 week after prophylaxis (meta-analysis pooled risk ratio [RR] = 0.17; 95% CI = 0.13–0.24) (6). No trials evaluated ceftriaxone or azithromycin against placebo, but two studies comparing rifampin with ceftriaxone found no statistically significant difference in eradication (RR = 3.71; 95% CI = 0.73–18.86) (6), and one study comparing azithromycin to rifampin reported no statistically significant difference in eradication (RR = 0.30; 95% CI = 0.30–5.54) (6,7). Across nine studies examining side effects and adverse events for at least one of the alternative antibiotics, reported adverse events were mild and included nausea, diarrhea, abdominal pain, headaches, dizziness, and skin rashes. Compared with rifampin, one study found a higher adverse event rate with ceftriaxone (RR = 1.39; 95% CI = 1.10–1.75); however, this difference was primarily driven by reports of pain at the injection site. Six studies reported on the antibiotic susceptibility of persistent isolates to at least one of the alternative antibiotics; development of resistance following prophylaxis was detected only for rifampin (6). Resistance to rifampin has also been reported in mass chemoprophylaxis settings, but because there is a fitness cost to the mutations associated with resistance, resistant strains have not become widespread (8); occasional rifampin prophylaxis failures have also been reported (9). CDC experts reviewed the literature since 2013 for updated data on the effectiveness of alternative prophylaxis regimens; no new data were identified.

The CDC expert group also considered adherence, acceptability, contraindications, and dosing regimens for the alternative antibiotics and noted that despite limited evidence of effectiveness, azithromycin would likely be the logistically simplest replacement for ciprofloxacin among the existing recommended prophylaxis options. In determining the duration of guidance, feasibility and communication challenges were considered, recognizing that frequent changes in recommended prophylaxis antibiotics within a local area might cause confusion among providers and public health staff members and might lead to lack of adherence. Flexibility in guidance criteria to allow for unique jurisdictional and cross-jurisdictional considerations during implementation, particularly when defining a catchment area, was emphasized in feedback discussions.